1. Fields of the Invention
This invention relates to a process for producing optically active alcohols by a biochemical method in which secondary alcohols are reacted with triglycerides in the presence of enzymes.
2. Description of the Prior Art
Optically active alcohols are known as chemical compounds which have a great demand as physiologically active substances, such as medical supplies, agricultural chemicals and so on, or as intermediates.
However, secondary alcohols represented by the formula: ##STR2## wherein X indicates an alkyl group having a carbon number of 2-10, Y indicates an alkyl group having a carbon number of 1-3, CF.sub.3 or CN, and X.noteq.Y, have optical isomers, so that these alcohols do not sufficiently exhibit activity in many cases unless either the R- or S-alcohol is in pure form.
For the above reason, in order to obtain optically active substances, it is necessary to optically resolve racemates which are obtained by a common method of synthetic chemical preparation, to conduct asymmetric synthesis or to synthesize in pare form from optically active materials by a stereochemical method.
Accordingly, it is desired to develop a technique for optically resolving the secondary alcohols by an industrially advantageous method.
The known optical resolution method of the secondary alcohols also needs complex steps and an expensive optical activator. For example, the salt is prepared by the steps in which 2-butanol or 2-octanol is reacted with phthalic acid, the obtained alkyl hydrogen phthalate is reacted with brucine, and the corresponding salt is repeatedly crystalized to resolve 2-butanol or 2-octanol. (Ref. Org. Syntheses, Coll. Vol. I, 418, 2nd ed., 1941).
Further, it is known that the optically active substances are obtained by optical resolution by biochemical methods.
For example, a method of Klibanov et al. (J. Am. Chem. Soc., 106, 2687 (1984)) uses yeast lipase or pig liver carboxy esterase dissolved in an aqueous buffered solution. In this case, unnecessary hydrolysis of triglyceride is unavoidable in the presence of moisture. Moreover, the enzyme is soluble in water and is unstable to moisture. In order to use the enzyme in a stable condition, it must be fixed on a polymer. In other words, one is unable to remove or reuse the enzyme unless it is fixed on the polymer.
There are biochemical methods in addition to the above method (Japanese Publication of Unexamined Patent Application No. Sho 59-205989 and others). In any case, one needs to use a buffered solution or lower alcohol, and an enzyme must be fixed on a carrier.
Klibanov et al. also reported a method in which enzyme powder was directly added to a reaction system (J. Am. Chem. Soc., 107, 7072 (1985)). In this case, heptane or ether is used as its solvent, and not triglyceride but monoester is used as an ester.
The present inventors have conducted research for resolving the above problems and for obtaining a process for producing an optically active secondary alcohol by an advantageous industrial method and have found that a racemic secondary alcohol of a raw material is efficiently resolved to an optically active aliphatic ester and its antipode, namely an optically active alcohol, by a biochemical transesterification reaction.